SCH708980 With and Without AmBisome for Visceral Leishmaniasis

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Sep 16, 2011

Keywords

ClinConnect Summary

Visceral leishmaniasis (VL) or kala-azar is the most severe form of leishmaniasis, which can be fatal if left untreated. The majority of VL cases are found in resource-poor regions, including India (Bihar), Bangladesh, Brazil, Nepal, and Sudan. VL pathogenesis has been linked to an overproduction of the anti-inflammatory cytokine, interleukin (IL)-10, which can promote parasite replication and disease progression. Experimental models have shown that IL-10 plays a key role in the pathogenesis of VL.

The current study has two parts. Part 1 will be an open-label, dose-escalating design to det...

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• Subjects (18 to 60 years of age) who meet the following criteria are eligible to enter the study:
• • Newly diagnosed VL (within 4 to 5 days of screening) and confirmed by spleen or bone marrow aspirate.
• • Clinical signs and symptoms compatible with VL: fever (\> 99 degrees F) over a 2-week duration, splenomegaly (palpable spleen below the costal margin), and weight loss.
• * Biochemical and hematological test values:
• • Hemoglobin \> 6.0g/100mL.
• • WBC count \> 1.0 times 10(9)/L.
• • Platelet count \> 40 times 10(9)/L.
• • Aspartate aminotransferase (AST),alanine transaminase (ALT), and alkaline phosphatase \< 3 times the upper limit of normal.
• • Prothrombin time (PT) \< 4 seconds above the control values.
• • Serum creatinine levels within normal limits (males, 0.7 mg/dL - 1.1 mg/dL; females, 0.6 mg/dL - 0.9 mg/dL).
• • Human immunodeficiency virus (HIV)-negative status.
• • Willingness to be hospitalized for 30 days.
• • Willingness to have samples stored.
• • Negative serum pregnancy test result for women of childbearing potential.
• EXCLUSION CRITERIA:
• • A history of intercurrent or concurrent diseases (e.g., chronic alcohol consumption or drug addiction; renal, hepatic, cardiovascular, or central nervous system disease; diabetes; tuberculosis or other infectious or major psychiatric diseases) that may introduce variables affecting the outcome of the study.
• • Any condition which, in the investigator's opinion, may prevent the subject from completing the study and the subsequent follow-up.
• • Previous treatment for VL within 45 days of study enrollment.
• • A history of allergy or hypersensitivity to amphotericin B.
• • Prior treatment failures with amphotericin B.
• • Current use of other drugs with known anti-leishmanial activity (e.g., antimonials, pentamidine, paromomycin, miltefosine), azoles (e.g., fluconazole, ketoconazole or itraconazole), nephrotoxic drugs, immunosuppressive drugs, other investigational agents, immunomodulatory drugs.
• • Breastfeeding women
• • Vaccinations within 30 days prior to enrollment in the study.
• Exclusion of children:
• • Subjects younger than 18 years of age will be excluded from the study because insufficient data are available supporting dosing with SCH708980 in adults to judge the potential risk in children.
• Exclusion of women:
• • Pregnant and lactating women are excluded from the study because insufficient data are available supporting dosing with SCH708980 in these populations to judge the potential risk.